The proposed research is designed to study the cellular and molecular basis of H-2 linked genetic control of immune responsiveness and immune suppression, and the role of I region in immunocompetent cell interaction. The primary goal is to test the hypothesis that I region gene products are a new class of antigen specific, cell surface receptor, expressed on macrophages, T cells, and B cells, and that they derive their specificity for antigen from amino acid sequence microheterogeneity among a large number of different I region gene products, as well as from different combinations of different I region gene products to produce molecules with apparent specificity for a wide range of foreign antigens. Allosera and monoclonal antibodies specific for restricted subregions of the I region will be produced in multiple donor-recipient combinations. These antisera will be used for determination of lymphoid cell types bearing Ia molecules, and for detection and mapping of functionally separate Ia clases of Ia molecules. These antibodies will also be used for isolating I region gene products for amino acid sequence studies and for immunoassays designed to detect in vitro translation of I region specific mRNAs isolated from murine spleen cells and murine lymphoid tumors expressing Ia antigens. Partially purified mRNA preparations will be utilized to produce cDNA molecules which will then be cloned to the pBR322 plasmid vector for cloning into E. coli. Resultant clones will be screened for expression of Ia antigens utilizing an immunoassay developed for detection and translation of eukaryotic gene products in E. coli and based on the use of antibodies to I region antigens. Once I region genes have been cloned into pBR322 they will be used for determination of Ia antigen DNA and amino acid sequence and for the production of probes to isolate genomic I region DNA. This will then permit an analysis of the genetic organization of the I region at the DNA level. Parallel studies will utilize a macrophage antigen presentation assay to determine the I region molecules which are required for successful presentation of antigen by macrophages to T cells. Attempts will then be made to achieve antigen presentation by membrane vesicles isolated from macrophage cell membranes or macrophage tumor cell membranes, and the results of these experiments will be used to develop liposomal model membrane systems incorporating known Ia antigen molecules to (Text Truncated - Exceeds Capacity)